This invention relates to a method of preparing 2-chloro-4-fluorophenol by direct chlorination of 4-fluorophenol.
2-Chloro-4-fluorophenol is useful as an intermediate material for medicines and agricultural chemicals since some derivatives of this compound exhibit remarkable physiological activities as represented by its 4-phenylurazole derivative.
Heretofore it has been believed to be difficult to substitute chlorine for hydrogen in the ring of 4-fluorophenol preferentially and exclusively at the 2-position. Accordingly, rather complicated substitution methods have been proposed for the preparation of 2-chloro-4-fluorophenol. According to J. Am. Chem. Soc., 81, 94 (1959), this compound is obtained through the steps of nitrating 4-fluoroanisole, aminating the nitro group by reduction, substituting the amino group by chlorine atom by the Sandmeyer reaction, and finally cleaving the ether bond. Though selective substitution at the 2-position is ensured, this method is not suited to industrial practice because of being a very roundabout process comprising various kinds of reactions. U.S.S.R. Pat. No. 154,250 proposes to obtain 2-chloro-4-fluorophenol by first chlorinating an alkali metal salt of 4-fluorophenol at its 2-position by using an alkali metal hypochlorite as the chlorinating agent. However, this method needs a complementary procedure to convert the chlorinated fluorophenolate into 2-chloro-4-fluorophenol, and the operations are troublesome.
To achieve direct chlorination of 4-fluorophenol at its 2-position, Zh. Obshch. Khim., 37, 2486(1967) shows the use of sodium hypochlorite or sulfuryl chloride as a chlorinating agent that is high in selectivity to the substitution at the 2-position. However, this simplified chlorination method cannot be regarded as an industrially profitable method because the yield of 2-chloro-4-fluorophenol based on 4-fluorophenol remains at a level of 82-92%.